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Find information on animal health topics, written for the veterinary professional.


By Dawn Merton Boothe, DVM, PhD, Department of Anatomy, Physiology, and Pharmacology, College of Veterinary Medicine, Auburn University

Chloramphenicol is a highly effective and well-tolerated broad-spectrum antibiotic. However, because it causes blood dyscrasias, it is prohibited for use in food-producing animals in several countries, including the USA and Canada. Thiamphenicol is less effective but safer than chloramphenicol; florfenicol, a thiamphenicol derivative, is significantly more active in vitro than chloramphenicol against many pathogenic strains of bacteria. Florfenicol is approved for use in cattle.

General Properties

Chloramphenicol is a relatively simple neutral nitrobenzene derivative with a bitter taste. It is highly lipid soluble and is used either as the free base or in ester forms (eg, the neutral-tasting palmitate for administration PO and the water-soluble sodium succinate for parenteral injection). Chloramphenicol is a relatively stable compound and is unaffected by boiling, provided that a pH of 9 is not exceeded. The nitrophenol group of chloramphenicol is replaced by a methyl sulfonyl group for thiamphenicol and florfenicol; florfenicol also contains a fluorine molecule. These structural changes improve efficacy, reduce toxicity, and for florfenicol, the fluorine molecule reduces bacterial resistance.

Antimicrobial Activity

Mode of Action:

The phenicols inhibit microbial protein synthesis by binding to the 50S subunit of the 70S ribosome and impairing peptidyl transferase activity. Because peptide-bond formation is inhibited, peptides cannot elongate. The effect is usually bacteriostatic but, at high concentrations, chloramphenicol may be bactericidal for some species. Protein synthesis is inhibited in both prokaryotic and eukaryotic (mitochondrial) ribosomes.

Bacterial Resistance:

Resistance against chloramphenicol develops slowly and in a stepwise fashion. In clinical bacterial isolates, high-level plasmid-mediated resistance reflects the production of chloramphenicol acetyltransferase (encoded for by the cat gene) and results in acetylation of the molecule, which can no longer bind to the ribosome. Other inactivating enzymes also may be involved. In resistant gram-negative bacteria, chloramphenicol acetyltransferase is a constitutive enzyme; in gram-positive organisms, the enzyme is inducible. The fluorine atom of florfenicol prevents acetylation, thus enhancing the efficacy of this drug. In Pseudomonas aeruginosa and in strains of Proteus and Klebsiella spp, resistance is also nonenzymatic and is based on an inducible permeability block that is both chromosomal and plasmid-mediated. Reduced permeability contributes to low level resistance. Very rarely, resistance may reflect altered ribosomal subunit structure and binding. Resistance to chloramphenicol often develops together with resistance to tetracycline, erythromycin, streptomycin, ampicillin, and other antibiotics because of multiple genes being carried on the same plasmid.

Antimicrobial Spectra:

Many genera of gram-positive and gram-negative bacteria and several anaerobes such as Bacteroides fragilis, as well as Rickettsia and Chlamydia spp are susceptible. Chloramphenicol is notable for its anaerobic spectrum. Of special note is the efficacy against many Salmonella spp but the resistance of most strains of P aeruginosa.

Pharmacokinetic Features


Absorption occurs promptly and rapidly from the upper GI tract when chloramphenicol base is administered PO to nonruminant animals. Blood concentrations usually are maximal in 1–3 hr. Because ruminal microflora readily reduce the nitro group, chloramphenicol is inactivated in the ruminoreticulum and is not available for absorption. The larger ester forms of chloramphenicol require hydrolysis by lipases to release the antibiotic for absorption from the GI tract; thus, the systemic availability of chloramphenicol is delayed when the palmitate and other ester preparations are used. Generic inequivalence has been seen with oral dosage forms. The presence of food and intestinal protectants does not interfere with absorption of chloramphenicol, although drugs that depress GI motility do. Florfenicol is rapidly absorbed after administration PO, although milk interferes with absorption.

Chloramphenicol sodium succinate may be injected both IV and IM. However, hydrolysis is required in the body because only free chloramphenicol base is active. The kinetics of this hydrolysis reaction may be slow and incomplete, with considerable individual and species variability. The absorption of chloramphenicol base itself from IM injection sites is notably restricted. For example, in horses, the therapeutic blood concentration of 5 mg/mL is achieved at a dosage of 50 mg/kg body wt, IM, after only 6–8 hr. Chloramphenicol base is absorbed after IP injection. Florfenicol is available as an injectable solution intended for IM use.


Approximately 40%–60% of chloramphenicol in plasma is reversibly bound to albumin, and the free fraction readily diffuses into almost all tissues (including the brain); highest concentrations are reached in the kidneys, liver, and bile. Substantial concentrations (~50% of plasma values) are also reached in many body fluids such as the CSF and aqueous humor. Milk concentrations are ~50% those of plasma but may be higher in mastitis. Transplacental diffusion is seen in all species, with concentrations of ~75% being reached in the fetus as compared with the dam. Chloramphenicol does not attain effective concentrations in normal synovial fluid but does so in septic arthritis. The blood-prostate barrier is an exception to the extensive intracorporeal distribution of chloramphenicol, and concentrations in the inflamed prostate are low to nil. Approximately 15%–20% of peak serum concentrations are seen within abscesses. Florfenicol also penetrates most body tissues, although penetration of CSF and aqueous humor is less than that of chloramphenicol. Florfenicol does penetrate the milk of lactating cows.


Unlike many other antibacterial agents, chloramphenicol undergoes extensive hepatic metabolism. Although some nitroreduction and other phase I reactions occur, free chloramphenicol is biotransformed primarily by glucuronide conjugation. Urinary products after administration of chloramphenicol sodium succinate include inactive forms, mainly the unhydrolyzed sodium succinate and the glucuronide; only 5%–15% appears as biologically active chloramphenicol.

There are several clinical concerns with respect to the biotransformation of chloramphenicol. In cats, a characteristic genetic deficiency in glucuronyl transferase activity leads to plasma half-lives that are often considerably longer than those in other species (eg, cats, 5.1 hr; ponies, 54 min), and dosages need to be adjusted accordingly. Phase I metabolism may also be deficient in cats. Very young animals frequently do not have full microsomal enzyme capabilities, and the plasma half-lives of chloramphenicol in the young (<4 wk old) of many species are often much longer than those of adults. Foals appear to be a notable exception to this generalization. Liver disease also prevents chloramphenicol from undergoing normal metabolic degradation, and active antibiotic accumulates in the body.


The principal route of excretion of parent drug (minor) and glucuronide is renal. Free chloramphenicol and the chloramphenicol sodium succinate dosage form undergo glomerular filtration (5%–10%), whereas the glucuronide metabolite is eliminated by tubular secretion (90%–95%). Only 5%–15% of chloramphenicol is present in the urine in the active, unchanged form. The biliary route also plays a part in excretion, but enterohepatic cycling is often pronounced, and usually only a small amount of chloramphenicol is recoverable in feces. Enterohepatic cycling prolongs blood concentrations to some degree in herbivores.

Pharmacokinetic Values:

The plasma half-life of chloramphenicol varies among species and depends on age in some species. The specific volumes of distribution usually reflect the extensive diffusion into tissues (see Table: Elimination and Distribution of Chloramphenicol and Florfenicol). Dose rates and frequencies are typically adjusted for the species and age of the animal. Florfenicol is eliminated by the kidneys.

Elimination and Distribution of Chloramphenicol and Florfenicol



Elimination Half-life (hr)

Volume of Distribution (mL/kg)








Calves (<1 wk old)













Therapeutic Indications and Dose Rates

Chloramphenicol is used to treat both systemic and local infections. Salmonellosis and Bacteroides sepsis have been specific indications, but use of chloramphenicol has decreased in the absence of an easily accessible, commercially available, approved preparation. Florfenicol is approved for use in treatment of bovine respiratory disease.

General dosages for chloramphenicol and florfenicol are listed in Dosages of Chloramphenicol and Florfenicol. The dose rate and frequency should be adjusted as needed for the individual animal.

Dosages of Chloramphenicol and Florfenicol



Dosage, Route, and Frequency



45–60 mg/kg, PO, IV, or IM, bid


45–60 mg/kg, PO, IV, or IM, tid-qid


50 mg/kg, PO, tid-qid, or IV, every 2–4 hr



20 mg/kg, IM, repeated in 48 hr

Special Clinical Concerns

Adverse Effects and Toxicity:

In people, chloramphenicol (but not florfenicol) can produce two distinctive syndromes of bone marrow suppression. One form is characterized by nonregenerative anemia (with or without thrombocytopenia or leukopenia), increased serum iron, bone marrow hypocellularity, cytoplasmic vacuolization of blast cells and lymphocytes, and maturation arrest of erythroid and myeloid precursors. This suppression is dose-dependent and reversible. Daily doses of 50 mg/kg for 3 wk can produce similar effects in cats. Milder hematologic effects are evident in dogs at much higher daily dosages (225 mg/kg). Such blood dyscrasias may also be seen in susceptible neonatal animals given standard adult doses of chloramphenicol. This toxic effect is postulated to be due to interference with mRNA and protein synthesis in rapidly multiplying cells.

The second form of bone marrow suppression is an irreversible aplastic anemia that is not related to dose or duration and may appear after the drug has been discontinued. Peripheral blood showing pancytopenia may be associated with hypoplastic or aplastic bone marrow. The incidence is ~1:25,000–40,000. The aplastic anemia appears to reflect lack of the nitro group and, as such, does not cause aplastic anemia. Because tissue residues in food animals might induce aplastic anemia in people, use of chloramphenicol in food animals is prohibited in the USA and several other countries. A form of aplastic anemia, apparently a type of hypersensitivity reaction to chloramphenicol, has been recognized in dogs and cats.

GI disturbances can develop in all nonruminant animals treated with oral chloramphenicol. Use in neonatal calves leads to a malabsorption syndrome associated with ultrastructural and functional changes of the small-intestinal enterocytes. Anorexia and depression have been seen in cats treated for >1 wk.

Because chloramphenicol can suppress anamnestic immune responses, animals should not be vaccinated while being treated with this antibiotic. Because of the ability of chloramphenicol to inhibit protein synthesis, excessive topical application on wounds may delay healing.

In both male and female rats, chloramphenicol has adversely affected the structure and functions of the gonads. In large animals, adverse signs are most often associated with propylene glycol–based preparations that, when infused rapidly IV, may result in collapse, hemolysis, and death.

Notwithstanding the severity of the chloramphenicol-associated adverse effects noted above, chloramphenicol is relatively safe, provided overdosage is avoided, courses of therapy are limited to 1 wk, the dose is reduced for newborn animals and for animals with impaired liver function, and there is no evidence of a preexisting bone marrow depression.


Chloramphenicol is a potent noncompetitive microsomal enzyme inhibitor that can substantially prolong the duration of action of several drugs administered concurrently. Frank toxic effects are likely if administration is repeated. Examples of such drugs include pentobarbital, codeine, phenobarbital, phenytoin, NSAIDs, and coumarins.

In combination with sulfamethoxypyridazine, chloramphenicol can cause hepatic damage. Chloramphenicol also delays the response of anemia to iron, folic acid, and vitamin B12. It interferes with the actions of many bactericidal drugs, such as the penicillins, cephalosporins, and aminoglycosides, and such combinations should not be used under most circumstances. Aqueous solutions of chloramphenicol sodium succinate should not be mixed with other preparations before administration because of a high incidence of incompatibility.

Chloramphenicol should not be administered concurrently with other antibacterial agents that bind to the 50S ribosomal subunit (eg, the macrolides and lincosamides).

Effects on Laboratory Tests:

Chloramphenicol may cause increased alkaline phosphatase concentrations and prothrombin times. WBC and thrombocyte counts may be decreased. Anemia becomes evident in extreme cases. A false glucosuria test is possible.

Drug Withdrawal and Milk Discard Times:

The use of chloramphenicol in food animals is prohibited in several countries including the USA; in others, withdrawal times vary considerably and may be as long as 2 wk. Withdrawal time for florfenicol is 28 days. Florfenicol should not be used in dairy cattle ≤20 mo old, veal calves, calves <1 mo old, or calves on an all-milk diet.

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